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Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism: A Randomized Trial

From Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts.

Acknowledgments: The authors are indebted to the 39 876 participants in the Women's Health Study for their dedicated and conscientious collaboration and to the entire staff of the study. They also thank Roche Molecular Systems for providing the genotyping platform used in the study.

In this large-scale, long-term trial of initially healthy women, 100 mg of aspirin on alternate days had little association with the overall rate of VTE and the rate of unprovoked VTE. The association of low-dose aspirin with the hazard of VTE was uniform during treatment and did not vary substantially across subgroups. No clear benefit of aspirin was observed among subgroups at particularly high risk for VTE who might benefit most from preventive therapies, although 95% CIs in some subgroups were wide.

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Aspirin and other antiplatelet drugs are highly effective at reducing major vascular events in patients who are at risk for or who have established atherosclerotic disease.1 Evidence suggests that antiplatelet agents can lower the risk for venous thromboembolism (VTE) in high-risk patients.2 Why aspirin is not effective for primary prevention of VTE in women at low to moderate risk as seen in the present study? Part of the answer to this question may be found in the differences in thrombus formation between the arterial and venous systems. The low-flow and low- pressure venous system is susceptible to reduced blood flow (stasis) and systemic activation of the coagulation cascade, as Virchow described more than 150 years ago, which predisposes to a thrombus even in a nonstenotic vessel. Most venous thrombi consist predominantly of red cells enmeshed in fibrin and contain relatively few platelets; hence, they have been described pathologically as "red thrombi." In contrast, in the high-flow and high-pressure arterial system, thrombi form under the influence of local shear forces, platelet activation, and exposure to thrombogenic substances on damaged vascular surfaces. Arterial thrombi, referred to as "white thrombi," typically are composed predominantly of platelets with relatively little fibrin or red-cell accumulation. Thus, it is plausible to expect that an anticoagulant would be used to prevent venous thromboemboli, whereas an antiplatelet agent would be used to prevent arterial thrombosis.3

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Summary for Patients

The summary below is from the full report titled “Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism. A Randomized Trial.” It is in the 16 October 2007 issue of Annals of Internal Medicine (volume 147, pages 525-533). The authors are R.J. Glynn, P.M Ridker, S.Z. Goldhaber, and J.E. Buring.

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